Experiments by many researchers have led to a picture of eucaryotic DNA as consisting primarily of interspersed repetitive and single copy sequences. Only a very small fraction of these sequences are transcribed. The available evidence suggests but does not prove that the primary transcription products in the nuclei of higher eucaryotes consist of large RNA precursor molecules which are processed to mRNA. The mRNA is then transported to the cytoplasm for translation into protein products. I have presented supportive evidence which indicates that regulation of gene expression in eucaryotes can occur at virtually any level (initiation of transcription, processing of RNA, translation of RNA, etc.). In addition, I have described several models for gene regulation, including some of my own, which attempt to explain the evidence via hypotheses that are testable by experiment. The globin systems of several animals are described since they offer a splendid opportunity to study gene regulaton. The globin mRNAs can be obtained fairly pure and in quantity. Furthermore the ontogeny of erythropoeisis can be studied, since the embryonic and fetal globins in some species have been well characterized. The recent development of recombinant DNA cloning, DNA sequencing, and HnRNA isolation techniques now makes it possible to consider the study of specific isolated control sequences and of HnRNA processing to be realistic objectives. I have accordingly designed a program involving the use of recombinant DNA plasmids to isolate sequences of interest which may then be studied by various hybridization experiments and by nucleotide sequencing. One very important area in my research program is the development of new gene isolation techniques making use of previously cloned chimeric plasmids. The work I am proposing will provide new information on genetic diseases, in particular, the thalassemias. The techniques and knowledge gained from this research on the relatively simple globin system can then be directly applied to the study of other genetic disorders, the immunoglobulin genes in myeloma cell lines, and eventually to integrated tumor virus genes.